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Expansion of the polyglutamine tract leading to protein aggregation and neuronal degradation has been linked to Machado\u2010Joseph disease\/spinocerebellar ataxia type 3, the most common form of dominantly inherited ataxia. In this study, we performed sequence self\u2010homology dot plot analysis and compared orthologous proteins to analyze the architecture of ataxin\u20103 during the evolution of Filozoa. This analysis uncovered up to three additional repetitions of the ubiquitin binding motif in ataxin\u20103, including the helical hairpin insertion in the Josephin domain, and revealed a highly conserved multimodular architecture that is broadly preserved throughout the Filozoa. Overall, a set of 78 putative ubiquitin binding repeats from 18 exemplar proteins were identified. Apparent neofunctionalization events could also be recognized, including modification of repeat 5 which gave rise to the disease\u2010linked polyglutamine tract, just before the Sarcopterygian divergence. 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